Transcript Slide 1

Crack is Whack
The Psycho-stimulant Cocaine
Biology of Toxins 445 - Toolson
Aaron Rivera, Sheila Rivera, Anabel Guerra
May 4, 2007
C17H21NO4
sweet lady cocaine
Powder cocaine
Chemical structure
Crack cocaine
Manufacture & Distribution



Cocaine comes from the Erythroxylum
plant and is manufactured by
converting tropinone into
2-carbomethoxytropinone, reducing
this to ecgonine, and then converting
the ecgonine to cocaine.
This isn't as easy as it sounds.
South Texas remains the leading entry
area for cocaine smuggled into the
United States.
Mexican DTOs have developed Atlanta
as a staging area for direct wholesale
cocaine distribution to East Coast drug
markets
Cocaine in the US
• the US government seized
153,000 lbs (69,000 kg) of cocaine
in 2006 but this is estimated to be
only 3-5%
• A conservative estimation of the
amount in circulation in the US
during 2006 is more than 3 million
lbs (1.4 million kg)
• 1 kg sells for approximately $20,000 in
today’s market
• the amount seized by the DEA is worth
approximately $1.4 billion which means
that the amount of cocaine in circulation
2006 was worth roughly $27 billion!!
Drug contamination of US
paper currency
Jenkins AJ.
Office of the Cuyahoga County Coroner,
11001 Cedar Road, 44106,
Cleveland, OH, USA
Forensic Sci Int 2001 Oct 1;121(3):189-93
ABSTRACT
It is known that US paper currency in the general circulation is contaminated with cocaine. Several
mechanisms have been offered to explain this finding, including contamination due to handling
during drug deals and the use of rolled up bills for snorting. Drug is then transferred from one
contaminated bill to others during counting in financial institutions. The possibility of contamination
of currency with other drugs has not been reported. In this study, the author reports the analysis of 10
randomly collected US$ 1 bills from five cities, for cocaine, heroin, 6-acetylmorphine (6-AM),
morphine, codeine, methamphetamine, amphetamine and phencyclidine (PCP). Bills were immersed
in acetonitrile for 2h prior to extraction and GC-MS analysis. Results showed that 92% of the bills
were positive for cocaine with a mean amount of 28.75+/-139.07&mgr;g per bill, a median of
1.37&mgr;g per bill, and a range of 0.01-922.72&mgr;g per bill. Heroin was detected in seven bills
in amounts ranging from 0.03 to 168.50&mgr;g per bill: 6-AM and morphine were detected in three
bills; methamphetamine and amphetamine in three and one bills, respectively, and PCP was detected
in two bills in amounts of 0.78 and 1.87&mgr;g per bill. Codeine was not detected in any of the US$
1 bills analyzed. This study demonstrated that although paper currency was most often contaminated
with cocaine, other drugs of abuse may be detected in bills.
The take-home thought is: the $1 bills in your wallet have a high probability
of cocaine contamination and you might just have other drugs on them too.
Factoids

A high from snorting may last 15-30 min while a high from
smoking cocaine may last only 5-10 min, so euphoria is
temporary either way
And Keep in Mind…
 0.5 kg will land a person 5 yrs in federal prison
 Cocaine is the no. 2 cause of drug-related emergency room
visits in the US
 National average of drug overdose is 7.1 deaths/100,000
people; NM is 11/100,000; Rio Arriba County is
33.1/100,000
Routes of Administration
• Injection
• Insufflation (snorting
or sniffing)
• Smoking
• Coca leaf infusions
• Chewing/Eating the
leaves
The Pope on Coke
His Holiness The Pope enjoyed the
invigorating properties of coca wine.
Leo XIII carried a personal hipflask
to fortify himself in time of need. A
grateful Pope awarded a Vatican gold
medal to its distinguished originator,
the Corsican-born pharmacist and
businessman, Angelo Mariani.
Mariani had a keen eye for the
benefits of celebrity-endorsement.
Drug Testing



Cocaine and benzoylecgonine, a cocaine metabolite, can
be detected in urine 2-4 days after the initial use; the
initial screening cutoff level is 300ng/ml
Chronic cocaine use can detected in the urine up to 3
weeks or longer depending on the individual
Hair samples can be taken to test for cocaine; typically
1.5 inches, starting at the root, is tested and cocaine use
can be revealed up to 90 days after use
Pharmacological Actions
Cocaine Affects
• the Central Nervous System
• the Cardiovascular System
• Skeletal Muscle
• Thermoregulation
• the Sympathetic Nervous System
• Local Actions
• the Eye
CNS Effects





Positron emission tomography scans showing the
average level of dopamine receptors in six
primates' brains. Red is high- and blue is lowconcentration of dopamine receptors. The higher
the level of dopamine, the fewer receptors there
will be. GVG is a drug typically used to treat
epilepsy however, it blocks cocaine’s action in the
brains of primates and is being tested as a
treatment for cocaine addiction in humans.

The first recognizable CNS action is on the
cerebral cortex
Cortical action is manifested as increased
motor activity
With small doses motor activity remains
coordinated, but as dosages increase lower
motor centers are affected causing tremors
and convulsive movements
Action of cocaine on the medulla results in
increased respiratory rate
The vasomotor and vomiting centers can be
stimulated and emesis is not uncommon
Central stimulation is soon followed by
depression of the vital medullary centers
which results in death due to respiratory
failure
Cardiovascular Systems Effects



Cocaine causes vasoconstriction which coupled with
tachycardia causes a rapid rise in blood pressure
Large IV doses of cocaine may result in immediate death
from cardiac failure due to direct toxic action on the heart
muscle
Topical application causes direct vasoconstriction of the
regional blood vessels
Effects on Thermoregulation


Cocaine is extremely pyrogenic
3 factors contribute to the rise in body temperature
1) Increased muscular activity augments heat
production
2) Vasoconstriction due to central vasomotor
stimulation decreases heat elimination
3) Direct action on the heat regulating centers
(hypothalamus)
Sympathetic Nervous System
& Skeletal Muscle Effects



Cocaine can potentiate the responses of sympathetically
innervated organs to epinephrine, norepinephrine and SNS
stimulation
Cocaine potentiates excitatory and inhibitory responses of muscles
and glands to epinephrine or adrenergic nerve impulses
There is no evidence that cocaine increases the strength of
muscular contraction therefore, it must be concluded that the
ability of the drug to delay fatigue results from central stimulation
which masks the sensation of fatigue
Local Actions




The most important local action of cocaine is its ability to
block nerve conduction when brought into direct contact
with nerve tissue (feelings of numbness)
Blocks terminal sensory nerve fibers in concentrations as
low as 0.02%
Higher concentrations are required to block conduction in
nerve trunks or to produce anesthesia by direct contact
Derivatives of cocaine, such as Novocain, are commonly
used today for their analgesic properties
Effects on eye





Ophthalmic application results in
anesthesia of the cornea, constriction
of the conjunctival vessels, and
blanched sclera
Anesthesia may also extend to the iris
Cocaine has varying effects on
intraocular pressure of the eye, in
most cases it is reduced via
vasoconstriction
Application to the eye occasionally
precipitates an attack of acute
glaucoma
Cornea may be come dry and
contaminated with foreign material.
Absorption and excretion






Local vasoconstriction limits cocaine’s rate of absorption;
despite this fact, the rate of absorption may easily exceed the
rate of detoxification and excretion
Cocaine is absorbed through all sites of application including
mucus membranes
Orally administered cocaine is hydrolyzed in the
gastrointestinal tract and rendered ineffective
After absorption cocaine is detoxified by the liver
It is estimated that the liver can detoxify one minimal lethal
dose in 60 minutes
Some maybe excreted unchanged in the urine
Addiction and Tolerance
“The cocaine addict is not a normal individual but is often a dangerous and
debased person. Many addicts become paranoid and suffer from ideas of
persecution, as a result they may carry weapons which they do not hesitate
to use. Addicts believe they are being threatened and have their thoughts
read by others.” -Louis S. Goodman, M.A., M.D., & Alfred Gilman, Ph.D, The
Pharmacological Basis of Therapeutics, 1955




Auditory, visual and tactual hallucinations are not uncommon
The sensation of something alive crawling on the skin is a
common complaint
In addition to mental deterioration the cocaine addict may
experience digestive disorders, nausea, loss of appetite,
emaciation, sleeplessness, tremors and occasionally
convulsions
Continued use of cocaine leads to tolerance
Mechanisms of Addiction & Tolerance




Cocaine binds to mesolimbic dopamine uptake transporter
proteins effectively blocking the reabsorption of dopamine
Dopamine stays in the synapse and stimulates the postsynaptic
receptor cells over and over again allowing the body to feel its
affects over a prolonged period
As reabsoption continues to be blocked, accumulated dopamine
in the synapses is washed away and degraded
Eventually the brain’s
dopamine supply becomes
inadequate to sustain a normal
mood; the synaptic bulb
cannot exocytose dopamine
fast enough to maintain
normal levels and pleasure
circuits go dry
Mechanisms of Addiction & Tolerance





Meanwhile, postsynaptic cell membranes become hypersensitive
and express new dopamine receptors
A viscous cycle is established: cocaine is needed to experience
pleasure but using it increases depletion of the neurotransmitter
Dopamine initially gets the brain’s attention causing glutamate to be
released in the pleasure center at 50-100% of the normal level
Repeated exposure to cocaine activates glutamate transmission and
prompts the synthesis of more glutamate receptors
Glutamate signaling seems to cause more permanent changes in the
brain (synaptic potentiation) that lead to compulsive drug seeking
behavior
Long-term Effects of Addiction
From snorting Loss of the sense of smell
 Nosebleeds
 Problems with swallowing
 Hoarseness
 Chronically runny nose
Actress Danniella Westbrook after years of cocaine use
 Perforated septum
From injecting May suffer severe allergic reactions
 Infection of the injection site
 Increased risk of contracting HIV and other blood-borne
diseases
To wrap it up folks just remember:
Blow No Mo’ cuz Crack Is Whack!
Bibliography







Goodman, Louis S. M.A., M.D., & Gilman, Alfred Ph.D (1956). The Pharmacological Basis
of Therapeutics (2nd ed.). New York: The MacMillan Company.
Marieb, Elaine N., R.N., Ph.D. (2004). Human Anatomy and Physiology (6th ed.). San
Francisco: Pearson Education, Inc.
National Institute on Drug Abuse (NIDA)
http://www.nida.nih.gov/ResearchReports/Cocaine/cocaine.html
http://www.drugabuse.gov/scienceofaddiction/
US Drug Enforcement Agency (DEA) http://www.usdoj.gov/dea/concern/18862/cocaine.htm
http://www.usdoj.gov/dea/concern/cocaine.html
United Nations Office of Drugs and Crime (UNODC)
http://www.unodc.org/unodc/world_drug_report.html
http://images.google.com/imgres?imgurl=http://www.med.umich.edu/opm/newspage/images
/vasoconstriction.jpg&imgrefurl=http://www.med.umich.edu/opm/newspage/2003/cocainehe
art.htm&h=180&w=240&sz=86&hl=en&start=6&um=1&tbnid=vXOLQrB_lCERbM:&tbn
h=83&tbnw=110&prev=/images%3Fq%3Dvasoconstriction%2Bfrom%2Bcocaine%26svnu
m%3D10%26um%3D1%26hl%3Den%26client%3Dsafari%26rls%3Den%26sa%3DN
http://www.erowid.org/chemicals/cocaine/cocaine_testing.shtml